{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:03:18Z","timestamp":1789736598093,"version":"4.0.1"},"reference-count":22,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt B"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    ATP9A, which belongs to the P4\u2010ATPase family of proteins, is involved in the efficient transport of vesicles from the Golgi apparatus to the plasma membrane, as well as the release of extracellular vesicles from human cells. In 2021, a loss\u2010of\u2010function variant of this gene was identified as being associated with a recessive neurodevelopmental disorder characterized by severe intellectual disability, motor delay, speech impairment, impaired fine motor skills, and behavioral anomalies, such as attention deficit hyperactivity disorder and aggressive behavior. Furthermore, in 2025, a de novo missense variant in the same gene was identified as being associated with a dominant neurodevelopmental disorder exhibiting a very similar phenotype. In this study, we identified three novel de novo variants in the\n                    <jats:italic>ATP9A<\/jats:italic>\n                    gene in two unrelated patients diagnosed with schizophrenia or schizoaffective disorder by performing trio short\u2010read whole\u2010genome sequencing (WGS). One individual presenting with severe psychosis was found to carry a de novo synonymous variant, c.2113C&gt;T, p.(Leu705=), in the\n                    <jats:italic>ATP9A<\/jats:italic>\n                    gene. All software predicted that this variant would alter the 5\u2032 splice site of intron 19. An intron minigene assay showed that it disrupts normal gene splicing. The second individual, who had refractory schizophrenia, was found to carry two variants in the\n                    <jats:italic>ATP9A<\/jats:italic>\n                    gene: a de novo nonsense variant c.1740C&gt;G, p.(Tyr580*), and a large de novo deletion including exons 18 and 19 of the\n                    <jats:italic>ATP9A<\/jats:italic>\n                    gene (GRCh38:g.51517885_51628972del). We demonstrated the presence of these two rare variants in cis using long\u2010range PCR. Our findings suggest that individuals with\n                    <jats:italic>ATP9A<\/jats:italic>\n                    gene variants may exhibit severe psychiatric disorders, regardless of the inheritance pattern. ATP9A plays a role in neuronal development and may therefore be involved in the development of psychiatric disorders. This warrants specific attention to heterozygous individuals. Our results reinforce the data obtained in the largest exome meta\u2010analysis conducted by the SCHEMA consortium. That study showed that protein\u2010truncating and pathogenic missense variants in\n                    <jats:italic>ATP9A<\/jats:italic>\n                    were significantly associated with schizophrenia (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.000372; odds Ratio\u2009=\u20095.48).\n                  <\/jats:p>","DOI":"10.1002\/ajmg.b.70036","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:10:36Z","timestamp":1789733436000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extending the\n                    <scp>ATP9A<\/scp>\n                    \u2010Related Phenotypic Spectrum: Indication of Schizophrenia Susceptibility"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0524-4827","authenticated-orcid":false,"given":"Camille","family":"Verebi","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Equipe Gorwood\/Ramoz  Paris France"},{"name":"Assistance\u2010Publique H\u00f4pitaux de Paris \u2013 Centre Universit\u00e9 de Paris, H\u00f4pital Cochin, Service de M\u00e9decine G\u00e9nomique des Maladies de Syst\u00e8me et d'Organe  Paris France"},{"name":"Laboratoire SeqOIA  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Louveau","sequence":"additional","affiliation":[{"name":"GHU\u2010Paris Psychiatrie et Neurosciences, H\u00f4pital Sainte\u2010Anne  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Diebold","sequence":"additional","affiliation":[{"name":"Assistance\u2010Publique H\u00f4pitaux de Paris \u2013 Centre Universit\u00e9 de Paris, H\u00f4pital Cochin, Service de M\u00e9decine G\u00e9nomique des Maladies de Syst\u00e8me et d'Organe  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natacha","family":"Gaitch","sequence":"additional","affiliation":[{"name":"Assistance\u2010Publique H\u00f4pitaux de Paris \u2013 Centre Universit\u00e9 de Paris, H\u00f4pital Cochin, Service de M\u00e9decine G\u00e9nomique des Maladies de Syst\u00e8me et d'Organe  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Hubas","sequence":"additional","affiliation":[{"name":"Assistance\u2010Publique H\u00f4pitaux de Paris \u2013 Centre Universit\u00e9 de Paris, H\u00f4pital Cochin, Service de M\u00e9decine G\u00e9nomique des Maladies de Syst\u00e8me et d'Organe  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine Gautier","family":"Vallee","sequence":"additional","affiliation":[{"name":"Assistance\u2010Publique H\u00f4pitaux de Paris \u2013 Centre Universit\u00e9 de Paris, H\u00f4pital Cochin, Service de M\u00e9decine G\u00e9nomique des Maladies de Syst\u00e8me et d'Organe  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Champ","sequence":"additional","affiliation":[{"name":"Laboratoire SeqOIA  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anais","family":"L'Haridon","sequence":"additional","affiliation":[{"name":"Laboratoire SeqOIA  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6668-8854","authenticated-orcid":false,"given":"Sophie Georgin","family":"Lavialle","sequence":"additional","affiliation":[{"name":"Assistance\u2010Publique H\u00f4pitaux de Paris, H\u00f4pital Tenon, Service de M\u00e9decine Interne, B\u00e2timent Gabriel  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1313-2788","authenticated-orcid":false,"given":"Boris","family":"Chaumette","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, NeuroDiderot (INSERM U1141), Institut Pasteur (CNRS UMR3571), GHU Paris Psychiatrie et Neurosciences  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5953-2728","authenticated-orcid":false,"given":"Thierry","family":"Bienvenu","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Equipe Gorwood\/Ramoz  Paris France"},{"name":"Assistance\u2010Publique H\u00f4pitaux de Paris \u2013 Centre Universit\u00e9 de Paris, H\u00f4pital Cochin, Service de M\u00e9decine G\u00e9nomique des Maladies de Syst\u00e8me et d'Organe  Paris France"},{"name":"Laboratoire SeqOIA  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"issue":"10","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2025.110631","article-title":"A Unique Gating Mechanism Revealed by the Cryo\u2010EM Structure of Monomeric ATP9A Flippase","volume":"301","author":"Abe K.","year":"2025","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3389\/fphys.2016.00275","article-title":"P4\u2010ATPases as Phospholipd Flippases\u2010Structure, Function, and Enigmas","volume":"7","author":"Andersen J. P.","year":"2016","journal-title":"Frontiers in Physiology"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201026273\u20100"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/humu\/7085599"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cimb43030125"},{"issue":"1","key":"e_1_2_10_7_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2024.108065","article-title":"Structural and Functional Properties of the N\u2010 and C\u2010Terminal Segments of the P4\u2010ATPase Phospholipid Flippase ATP8A2","volume":"301","author":"Matsell E.","year":"2025","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41525\u2010021\u201000255\u2010z"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010022\u201001940\u2010w"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010023\u201001961\u2010z"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0213069"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2024.101183"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"issue":"6","key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1080\/10409238.2016.1237934","article-title":"Decoding P4\u2010ATPase Substrate Interactions","volume":"51","author":"Roland B. P.","year":"2016","journal-title":"Critical Reviews in Biochemistry and Molecular Biology"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2011.12.007"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010022\u201004556\u2010w"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E16\u201008\u20100586"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms14047897"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102021\u2010107843"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8865499"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202403163"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033\u2010026\u201011496\u20105"},{"issue":"44","key":"e_1_2_10_23_1","doi-asserted-by":"crossref","first-page":"31807","DOI":"10.1074\/jbc.M113.481986","article-title":"Auto\u2010Inhibition of Drs2p, a Yeast Phospholipid Flippase, by Its Carboxyl\u2010Terminal Tail","volume":"288","author":"Zhou X.","year":"2013","journal-title":"Journal of Biological Chemistry"}],"container-title":["American Journal of Medical Genetics Part B: Neuropsychiatric Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.b.70036","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.b.70036","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.b.70036","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:10:37Z","timestamp":1789733437000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.b.70036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,18]]},"references-count":22,"alternative-id":["10.1002\/ajmg.b.70036"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.b.70036","archive":["Portico"],"relation":{},"ISSN":["1552-4841","1552-485X"],"issn-type":[{"value":"1552-4841","type":"print"},{"value":"1552-485X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,18]]},"assertion":[{"value":"2025-10-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ajmg.b.70036"}}